The primary goal of this research is to understand the structural basis for the toxicity of ricin OR, abrin A and abrin C, and the structural features in the bowman-Birk, type proteinase inhibitors. PI-I, PI-II and PI-V. These proteins have been crystallized to the optimal sizes for crystallographic studies. Their crystals diffract to at least 3 angstroms resolution for ricin OR, 3 angstroms for abrin C, 6 angstrom for abrin A, 1.8 angstroms for PI-I, 2.5 angstroms for PI-II and 2.5 angstroms for PI-V. For the toxic lectins (ricin OR, abrin A and C) we will determine their structures, study the relationships between the A and B-chains, compare the structural details between ricin OR and ricin D, and between ricin and abrin, and analyze how these macromolecules can penetrate the cell membrane. This information will be of vital importance to our understanding of the mechanism of toxicity in these proteins, and for aiding the design of hybrid toxins for target- specific cell destruction. The potential use of cell specific toxins are many, for example in the "toxosurgery" of cancer cells, the removal of lymphocytes of certain specificity for the acceptance of a tissue transplant, etc. For the Bowman-Birk type inhibitors we will determine their structures, compare the structures within this inhibitor family as well as with other families. Since the Bowman-Birk family represents a unique type of protein structure and the detailed architecture of this type has not been previously illustrated, the knowledge which will be gained from this research not only will increase our understanding on the structure-function relationship of proteinase inhibitors but also will widen our perspective on the basic folding patterns of proteins in general. The secondary goal of this research is to test and refine the iterative single isomorphous replacement and the iterative single anomalous scattering methods that the P.I. has recently developed for X-ray analysis of macromolecules. We will apply these new techniques to the determinations of the proposed protein structures. Our studies will increase the understanding of how to use these techniques optimally and where to make needed improvement.